EP0958789A2 - Apparatus for delivering antibiotic powders into the femoral canal - Google Patents

Abstract

Apparatus of the present invention include encapsulating the antibiotic in fineparticles of bioabsorbable polymer which will yield a constant dissolution of the antibiotic overa predefined dosing period (such as a 7-10 day period), with residual antibiotic being thereafterdelivered only until the bioabsorable polymer is resorbed; and delivering the fine particlepowder to the surgical site as an aerosol spray. It is preferable that the antibiotic and thepolymer be thermostable so that the exothermic reaction of bone cement does not degrade thepolymer or the antibiotic. A suitable antibiotic for this purpose is an aminoglycoside. Oneapparatus according to the invention includes a porous delivery tube which is dimensioned to fitcomfortable in a bone canal and which is coupled to a aerosol canister containing the antibioticpowder of the invention. Another apparatus according to the invention includes a porousdelivery tube which is preloaded with measured amounts of antibiotic powder and which isadapted to be coupled to a source of compressed air.

Description

TECHNICAL FIELD
• The invention relates to apparatus for dispensing medication at a surgical site. Moreparticularly, the invention relates to apparatus for dispensing antibiotics at an orthopaedicsurgical site.
BACKGROUND OF THE INVENTION
• In open surgical procedures, it is common to apply an antibiotic, analgesic, growth stimulator,or other chemical agent at the surgical site prior to closing the incision in order to controlinfection, decrease pain, promote growth, etc.
• One of the most devastating complications of total joint arthroplasty is deep sepsis. Treatmentof an infected joint replacement is difficult due to its location, and localized devascularizationresulting from this procedure.
• Current approaches to therapy for deep infections include systemic or parenteral antibioticregimes, and the use of antibiotic impregnated acrylic bone cement. Due to the localizeddevascularization it is difficult to achieve therapeutic levels in the bone surrounding the implantwithout exceeding toxic serum concentrations when utilizing systemic or parenteral treatments.The use of antibiotic containing bone cement results in high local concentrations, whileavoiding toxic serum levels, but the antibiotic has been shown to elute in trace quantities forextended periods of time (greater than one year). Residual trace amounts of antibiotics haveraised concerns of resistant strain formation. An additional concern regarding addingantibiotics to bone cement is the possible degradation of mechanical properties of the bonecement whose primary function is as a fixation material.
• According to the state of the art, it is preferable to apply therapeutic concentrations at thesurgical site for a period of 7 to 10 days, with no residual antibiotics lingering for extended periods of time. It is also desirable to achieve these high local concentrations without elevatingserum concentrations, thus reducing the threat of systemic toxicity. A means of antibiotictreatment that can be utilized for joint replacement procedures that either involve the use ofbone cement or not is desirable as well.
• U.S. Patent Number 5,681,289 to Wilcox et al. discloses a dispensing bladder for passing a lowvolume flow of a liquid chemical agent at an orthopaedic surgical site. The bladder is installedadjacent to or as part of an orthopaedic implant. It is coupled to a tube which receives a supplyof liquid chemical such as an antibiotic via an injection port or an implanted or externalreservoir and pump.
• The bladder may be biodegradable so as to avoid the need for extensive surgery to remove it.However, the tube, injection site, pump, and reservoir must be surgically removed. Moreover,it is believed that the delivery of a liquid antibiotic in the femoral canal may degrade themechanical properties of bone cement on an implant stem.
SUMMARY OF THE INVENTION
• It is therefore an object of the invention to provide apparatus for delivering an antibiotic to anorthopaedic surgical site.
• It is also an object of the invention to provide apparatus for delivering an antibiotic to anorthopaedic surgical site which does not require an additional implant which must subsequentlybe surgically removed.
• It is another object of the invention to provide apparatus for delivering an antibiotic to anorthopaedic surgical site which will deliver a therapeutic dose of antibiotic over a predefineddosing period, for example 7-10 days.
• It is still another object of the invention to provide apparatus for delivering an antibiotic to anorthopaedic surgical site which will not interfere with the mechanical properties of bonecement.
• Another object of the invention is to provide apparatus for delivering an antibiotic to anorthopaedic surgical site which does not leave long term residual antibiotics at the site after thedosing period.
• Another object of the invention is to provide apparatus for delivering an antibiotic to anorthopaedic surgical site which do not significantly elevate serum levels.
• In accord with these objects which will be discussed in detail below, the apparatus of thepresent invention includes means for encapsulating the antibiotic in fine particles ofbioabsorbable polymer which will yield a constant dissolution of the antibiotic over apredefined dosing period (such as a 7-10 day period), with residual antibiotic being thereafterdelivered only until the bioabsorable polymer is resorbed; and means for delivering the fineparticle powder to the surgical site as an aerosol spray.
• It is preferable that the antibiotic and the polymer be thermostable so that the exothermicreaction of bone cement does not degrade the polymer or the antibiotic.
• A suitable antibiotic for this purpose is an aminoglycoside and a suitable polymer is polylactide-coglycolide (PLGA).
• In situations where themostability is not an issue, for example where bone cement is not used,then virtually any antibiotic may be delivered via the techniques taught herein, such as (withoutlimitation), penicillin, etc. Furthermore, those skilled in the art will readily appreciate that otherbioabsorable polymers can be readily substituted for PLGA, for example (without limitation),PLA, etc.
• One apparatus according to the invention includes a porous delivery tube which is dimensionedto fit comfortably in a bone canal and which is coupled to a aerosol canister containing theantibiotic powder of the invention.
• Another apparatus according to the invention includes a porous delivery tube which is pre-loaded with measured amounts of antibiotic powder and which is adapted to be coupled to asource of compressed air.
• Additional objects and advantages of the invention will become apparent to those skilled in theart upon reference to the detailed description taken in conjunction with the provided figures.
BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1

is a schematic sectional view of a first embodiment of an antibiotic delivery apparatusaccording to the invention;

FIG. 2

is a schematic perspective view of a second embodiment of an antibiotic deliveryapparatus according to the invention; and

FIG. 3

is an enlarged perspective view of a component of the antibiotic delivery apparatus ofFIG. 2.

DETAILED DESCRIPTION
• According to the invention, a powdered antibiotic is manufactured by encapsulating antibioticin fine particles of bioabsorbable polymer.
• Suitable processes for encapsulating an antibiotic in a resorbable powder are disclosed in thefollowing nine journal articles, the complete disclosures of which are hereby incorporatedherein by reference:
• (a) Van Hamont, J.E. et al., "Evaluation of Solvent Extraction and SolventEvaporation Procedures for Production of Tobramycin-Releasing Microspheres," Proceed.Intern. Symp. Control. Rel. Bioact. Mater., 23 (1996), Controlled Release Society, Inc.
• (b) Martinez, B. et al., "Tetracine Release from Biodegradable Microspheres,"Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 27 (1997), Controlled Release Society,Inc.
• (c) Kim, J.H. et al., "The Modified Solvent Extraction Method on the Preparation of Poly(L-Lactic Acid) Microspheres," Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 24(1997), Controlled Release Society, Inc.
• (d) Bittner, B. et al., "Preparation of Protein-Loaded Poly(Lactide-Co-Glycolide)Microspheres Using an Ultrasonic Atomizer." Proceed. Intern. Symp. Control. Rel.BlioaCt. Mater., 24 (1997), Controlled Release Society, Inc.
• (e) Takada. S., "Novel Microencapsulation Technique for Controlled Release of aWater-Soluble Non-Basic Drug," Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 23(1996), Controlled Release Society, Inc.
• (f) Jeyanthi, R. et al., "Novel Burst Free Programmable BiodegradableMicrospheres for Controlled Release of Polypeptides," Proceed. Intern. Symp. Control. Rel.Bioact. Mater., 23 (1996), Controlled Release Society, Inc.
• (g) Witschi, C., "Influence of the Preparation Method and Polymer Composition onPeptide Adsorption and Peptide Release from Biodegradable Microparticles During In VitroRelease," Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 24 (1997), ControlledRelease Society, Inc.
• (h) Van Hamont, J.E. et al., "Effect of PLGA End Groups on Encapsulation andRelease of Tobramycin from Microspheres Produced by Organic Processes," Proceed. Intern.Symp. Control. Rel. Bioact. Mater., 24 (1997), Controlled Release Society, Inc.
• (i) Grandfils, C. et al., "Control of the Biodegradation Rate of Poly(DL-Lactide) Microparticles Intended as Chemoembolization Materials," Journal of Controlled Release 38(1966).
• The prepared antibiotic powder. when placed at a surgical site will yield a constant dissolutionof the antibiotic over a period of 7-10 days.
• Turning now to FIG. 1, anapparatus 10 according to the invention for delivering the powderedantibiotic to an orthopaedic surgical site includes aporous tube 12 which is coupled to anaerosol container 14 which contains a measured amount of the powdered antibiotic for a singleprocedure.
• According to a presently preferred illustrative embodiment, thetube 12 is dimensioned to fitcomfortable in theintermedullary canal 16 of thefemur 18. Thetube 12 is made of abiocompatible material such as plastic or stainless steel and is made porous byperforations 12awhich are evenly spaced about thetube 12.
• The apparatus is used during an orthopaedic procedure after thefemoral canal 16 is prepared,before the prosthetic implant is installed.
• Theapparatus 10 is operated by inserting thetube 12 into theIM canal 16 of thefemur 18 andopening a valve (not shown) on theaerosol container 14.
• The aerosol forces the antibiotic powder into thetube 12 and out through theperforations 12a into the wall of theIM canal 16.
• According to a presently preferred embodiment. theaerosol container 14 contains enoughpowder and propellant for one application and is disposable after one use. After the aerosol isdepleted, theapparatus 10 is removed from the femur and the prosthetic implant is installed in aconventional manner.
• The antibiotic powder which was delivered to the IM canal will not interfere with bone cement,will dissolve a therapeutic level of antibiotic into the femur continuously over 7-10 days andwill not leave long time residual antibiotics in the femur.
• Turning now to FIGS. 2 and 3, anotherapparatus 20 according to the invention includes aporous delivery tube 22 which is pre-loaded with measured amounts ofantibiotic powder 26and which is adapted to be coupled to a source ofcompressed air 30.
• Thetube 22 may be made of biocompatible plastic or stainless steel which may be made porousbyperforations 22a which are evenly spaced along the length of the tube.
• According to this illustrative embodiment of the invention, a plurality of annular shelves 24(e.g., 24a-24j) are arranged inside thetube 22 axially spaced apart from each other as shown inFIG. 2. Eachshelf 24 carries a measured amount ofantibiotic powder 26 as shown in FIG. 3.
• According to a preferred embodiment, eachshelf 24 has a plurality oforthogonal fins 28 which aid in stacking the shelves inside thetube 22 and directing the flow ofpowder 26 out of theperforations 22a.
• Theapparatus 20 is operated by inserting thetube 22 into the IM canal of the femur, attaching asource 30 of compressed air to the tube and forcing compressed air into the tube. Thecompressed air forces theantibiotic powder 26 off of theshelves 24 and out through theperforations 22a into the wall of the IM canal.
• According to a presently preferred embodiment, theshelves 24 containenough powder 26 forone application and theapparatus 20 is disposable after one use. After a measured period ofdispensing, theapparatus 20 is removed from the femur and the prosthetic implant is installed ina conventional manner.
• The antibiotic powder which was delivered to the IM canal will not interfere with bone cement,will dissolve a therapeutic level of antibiotic into the femur continuously over 7-10 days andwill not leave long time residual antibiotics in the femur.
• There have been described and illustrated herein several embodiments of a method andapparatus for delivering antibiotic powder to the IM canal of the femur.
• While particular embodiments of the invention have been described, it is not intended that theinvention be limited thereto, as it is intended that the invention be as broad in scope as the artwill allow and that the specification be read likewise. Thus, while particular powders have been disclosed, it will be appreciated that other powders could be utilized. Also, while the inventionhas been disclosed for use in the IM canal of the femur, it will be understood that the inventionmay have utility in dispensing medication in other bone canals.
• It will therefore be appreciated by those skilled in the art that yet other modifications could bemade to the provided invention without deviating from its scope as so claimed.

Claims (18)

1. An apparatus for dispensing medication into a bone canal, said apparatus comprising:

   (a) a porous tube dimensioned to fit into the bone canal:

   (b) a powdered medication deliverable through said porous tube; and

   (c) fluid pressure means coupled to said tube means for forcing said powdered medicationthrough said porous tube.
2. An apparatus according to claim 1 wherein said fluid pressure means comprises anaerosol container and said powdered medication is contained within said aerosol container.
3. An apparatus according to claim 1 or 2, wherein said powdered medication is containedwithin said porous tube and said fluid pressure means is detachable from said porous tube.
4. An apparatus according to any one of claims 1 to 3, wherein said porous tube includes aplurality of annular shelves and said powdered medication is contained on said shelves.
5. An apparatus according to claim 4 wherein each of said annular shelves has a pluralityof orthogonal vanes.
6. An apparatus according to any one of the preceding claims, wherein said powderedmedication is an antibiotic encapsulated in a bioabsorbable polymer in such a way as to yieldconstant dissolution over a predefined therapeutic dosing period with residual antibiotic being delivered thereafter only until said bioabsorbable polymer is resorbed.
7. Apparatus as set forth in claim 6 wherein said predefined therapeutic dosing period is 7-10days.
8. An apparatus according to claim 1 wherein said powdered medication is thermostablewhen exposed to an exothermic reaction of orthopaedic bone cement.
9. An apparatus according to claim 7 wherein said antibiotic is an aminoglycoside.
10. An apparatus according to claim 7 wherein said bioabsorbable polymer is poly lactide-co-glycolide(PLGA).
11. An apparatus for dispensing medication into a bone canal, said apparatus comprising:

    (a) a porous tube dimensioned to fit into the bone canal;

    (b) an aerosol container coupled to said porous tube; and

    (c) a powdered medication contained in said aerosol container and deliverable throughsaid porous tube.
12. An apparatus according to claim 11 wherein said porous tube is one of a perforateplastic tube and a perforate stainless steel tube.
13. An apparatus according to claim 11 or 12, wherein said powdered medication is an antibiotic encapsulated in a bioabsorbable polymer in such a way as to yield constantdissolution over a predefined therapeutic dosing period with residual antibiotic being deliveredthereafter only until said bioabsorbable polymer is resorbed.
14. Apparatus as set forth in claim 13 wherein said predefined therapeutic dosing period is7-10 days.
15. An apparatus according to claim 11 wherein said powdered medication is thermostablewhen exposed to an exothermic reaction of orthopaedic bone cement.
16. An apparatus according to claim 13 wherein said antibiotic is an aminoglycoside.
17. An apparatus according to claim 13 wherein said bioabsorbable polymer is poly lactide-co-glycolide(PLGA).
18. An apparatus for dispensing medication into a bone canal, said apparatus comprising:

    (a) a porous tube dimensioned to fit into the bone canal;

    (b) a powdered medication deliverable through said porous tube, said powdered medication beingdisposed in a plurality of locations within said tube; and

    (c) fluid coupling means for coupling said tube to a source of fluid pressure for forcing saidpowdered medication through said porous tube.

Images